Superparamagnetic iron oxide nanoparticles development, characterization, cupper-64 labeling and cellular tracking

Development of nanostructures as MR contrast agent will significantly improve the field of disease diagnostics. Contrast agents such as iron oxide nanoparticles are less toxic compared to more commonly used gadolinium based agents. A subclass of iron based nano particles are super paramagnetic iron oxide nano particles, (SPIOs) which are widely studied MR contrast agents useful in both imaging and drug delivery applications. In this work, SPIOs were synthesized and characterized and used for cellular tracking and multi modal labeling. A new solvent exchange method was utilized to coat different core size iron oxide nano particles. SPIOs were characterized for in-vivo imaging using MR and they had a very uniform size distribution which was determine using dynamic light scattering (DLS) and transmission electron microscopy. Furthermore, blood circulation half-life of 16nm SPIOs were determined through tail vein injection. SPIOs have many applications among which is the in vivo tracking of stem cells which is critical for determination of stem cells fate after injection. Magnetic Resonance (MR) as a non-invasive method can provide significant information about the fate of the cells as well as determination of the success rate of therapeutic cellular deliveries. Mesenchymal stem cells can be loaded with super paramagnetic iron oxide nano particles (SPIOs) and have their movements followed once planted in vivo. We present our findings on the effect of SPIO concentration and stem cell density on the MR signal and transverse relaxation time. Our preliminary results indicated that SPIOs do not cause mesenchymal stem cell cytotoxicity and do not affect proliferation ability up to 200 μg/ml concentration. The release of the nanoparticles was investigated 24 hours post internalization and the result showed that SPIOs will stay inside the cell. We also found that the contrast increases in a concentration dependent manner. Our results suggest that using MR with low concentration of SPIOs is a novel and promising method for tracking of mesenchymal stem cells. In this work SPIOs were also labeled with 64Cu to investigate their potential for multi modal positron emission tomography (PET) MR imaging. Dual modality PET MR SPIO contrast agent can be synthesized to image diseases such as cancer and atherosclerosis. The advantage is the non-invasive and early detection of disease at molecular lever before it has spread to late stages or in case of the atherosclerosis before the plaque has blocked the vessel. To develop a multi modal contrast agent, a positron emitter, 64Cu (half-life of 12.701 ± 0.002 hours), was used in labeling and synthesis was performed all in one step with the addition of 64Cu chelator, 14-PE DTPA followed by radiolabeling for both 6.5nm SPIO and 17nm SPIO. After labeling and purification with the desalting column, the amount of dissociated 64Cu in the solution was determined using radio thin layer chromotagraphy (TLC) and the particle was shown to have minimum amount of fee 64Cu. Serum stability of labeled SPIO was determined in vitro by incubating 64Cu-labeled SPIOs in mouse serum at 37 °C for 24 hr with constant shaking. Radio TLC result then revealed that 64Cu stays bounded to the SPIO after 24 hours in mouse serum. This means that 64Cu labeled SPIO has a great potential as a dual modality contrast agents and further in-vivo studies are required to verify the findings.MSCommittee Chair: Bao, Gang; Committee Member: Fox, Tim; Committee Member: Rahnema, Farza

PET/MR imaging of atherosclerotic plaque and tumor using dual modality SPIOS

Early stage disease diagnosis still remains a challenge despite much efforts to develop novel imaging and diagnostic techniques. Nanoparticles used as molecular imaging contrast agents with multifunctionality and flexibility provide a platform for targeting the specific disease biomarkers and integration of imaging modalities. In this work, we developed a simplified method for synthesis of radiolabeled targeted super paramagnetic iron oxide nanoparticles (SPIOs). This method takes advantage of the chelator BAT that is conjugated to the PEG before the coating process begins. The effect of nanoparticle size and PEG density was investigated in a series of in vivo experiments. The 64Cu-VINP-SPIOs were used in the PET imaging of inflammation and 64Cu-CD105-SPIOs were used in imaging of 4T1 murine tumor model. In summary, we investigated the potential of the radiolabeled, targeted SPIOs in imaging atherosclerotic plaque and tumor in vivo using magnetic resonance imaging (MRI) and Positron emission tomography (PET). Our results show that dual modality SPIOs with active targeting mediated by affinity ligands can be a great tool in molecular imaging and diagnosis of early stage plaque and tumor.Ph.D

Biological synthesis of nanowires: conducting polymers for nanomedicine

Presented on February 28th, 2012 from 11:00 am - 12:30 pm in the Georgia Tech Library, Neely Lobby, 1 WestPanelists: Dr. Adegboyega "Yomi" Oyelere -- Assistant Professor of Chemistry and Biochemistry; Dr. Steven Hira -- post-doctoral researcher in the laboratory of Dr. Christine Payne, Assistant Professor of Chemistry and Biochemistry; Nazanin Masoodzadehgan -- graduate student in the laboratory of Dr. Gang Bao, Professor of Biomedical Engineering.Runtime: 71:36 minutes.Panelists will be discussing the use of gold nanoparticles for targeted drug delivery into tumor cells, intracellular synthesis of conducting polymer nanowires, and the use of magnetic iron oxide nanoparticles as MRI contrast agents and hyperthermia agents for cancer cells. This is the fourth installment of the Blended Research Series presented by the Faculty Engagement Department. The Blended Research Series is a panel discussion series focusing on multidisciplinary research. At each session, faculty and graduate students from various departments present research in an area that crosses over multiple discipline